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Epidermal 1-O-acylc...
Epidermal 1-O-acylceramides appear with the establishment of the water permeability barrier in mice and are produced by maturating keratinocytes
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Rabionet, Mariona (author)
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Bernard, Pauline (author)
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Pichery, Melanie (author)
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Marsching, Christian (author)
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Bayerle, Aline (author)
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Dworski, Shaalee (author)
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Kamani, Mustafa A. (author)
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Chitraju, Chandramohan (author)
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Gluchowski, Nina L. (author)
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Gabriel, Katlyn R. (author)
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- Asadi, Abolfazl (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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Ebel, Philipp (author)
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Hoekstra, Menno (author)
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Dumas, Sabrina (author)
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Ntambi, James M. (author)
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- Jacobsson, Anders (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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Willecke, Klaus (author)
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Medin, Jeffrey A. (author)
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Jonca, Nathalie (author)
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Sandhoff, Roger (author)
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(creator_code:org_t)
- 2022-03-23
- 2022
- English.
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In: Lipids. - : Wiley. - 0024-4201 .- 1558-9307. ; 57:3, s. 183-195
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
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- 1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. Here we show epidermal 1-OACs arise shortly before birth during the establishment of the water permeability barrier in mice. Fractionation of human epidermis indicates 1-OACs concentrate in the stratum corneum. During in vitro maturation into reconstructed human epidermis, human keratinocytes dramatically increase 1-OAC levels indicating they are one source of epidermal 1-OACs. In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). Overall levels of 1-OACs did not decrease in any mouse model. In Cers3 and Dgat2-deficient epidermis they even increased in correlation with deficient skin barrier function. Dagt2 deficiency reshapes 1-OAC synthesis with an increase in 1-OACs with N-linked non-hydroxylated fatty acids and a 60% decrease compared to control in levels of 1-OACs with N-linked hydroxylated palmitate. As none of the single enzyme deficiencies we examined resulted in a lack of 1-OACs, we conclude that either there is functional redundancy in forming 1-OAC and more than one enzyme is involved, and/or an unknown acyltransferase of the epidermis performs the final step of 1-OAC synthesis, the implications of which are discussed.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Keyword
- acyl
- acyltransferase
- Asah
- brain
- ceramides
- Dga1p
- Dgat2
- epidermis
- Farber disease
- heart
- kidney thymus
- Lcat
- liver
- Lpla2
- Lro1p
- lung
- lymph node
- mammals
- skin barrier
- spleen
Publication and Content Type
- ref (subject category)
- art (subject category)
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Lipids
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- By the author/editor
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Rabionet, Marion ...
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Bernard, Pauline
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Pichery, Melanie
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Marsching, Chris ...
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Bayerle, Aline
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Dworski, Shaalee
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show more...
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Kamani, Mustafa ...
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Chitraju, Chandr ...
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Gluchowski, Nina ...
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Gabriel, Katlyn ...
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Asadi, Abolfazl
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Ebel, Philipp
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Hoekstra, Menno
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Dumas, Sabrina
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Ntambi, James M.
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Jacobsson, Ander ...
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Willecke, Klaus
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Medin, Jeffrey A ...
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Jonca, Nathalie
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Sandhoff, Roger
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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Lipids
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Stockholm University